Countering Oxidative Stress In The Retina With The Ubiquitin System
We have developed a protein-based therapeutic treatment that increases the ability of cells to eliminate ROS and thereby reduces oxidative stress. We are targeting this protein directly to the RPE cells and photoreceptors of mice by sub-retinally injecting (delivering through a needle to a point just under the retina) adeno-associated viruses (AAVs) that express the therapeutic protein. AAVs have been used safely and successfully in eye gene therapy clinical trials. We have made significant progress during the initial phase of this project in 2009. In collaboration with Dr. William Hauswirth (at University of Florida), we have generated highly purified and concentrated AAVs that express our therapeutic protein. Further, we have sub-retinally injected the viruses into mouse eyes to determine how much time it takes for the therapeutic protein to be expressed and to establish a safety profile for expression of the protein in the retina.
Plafker KS, Singer JD, Plafker SM. The ubiquitin conjugating enzyme, UbcM2, engages in novel interactions with components of cullin-3 based E3 ligases. Biochemistry 48:3527-3537, 2009.
Plafker KS, Nguyen L, Barneche M, Mirza S, Crawford D, Plafker SM. The ubiquitin-conjugating enzyme UbcM2 can regulate the stability and activity of the antioxidant transcription factor Nrf2. J Biol Chem 285:23064-23074, 2010.
Plafker SM. Oxidative stress and the ubiquitin proteolytic system in agerelated macular degeneration. Adv Exp Med Biol 664:447-456, 2010.
Mirza S, Plafker KS, Aston C, Plafker SM. Expression and distribution of the class III ubiquitin-conjugating enzymes in the retina. Mol Vis 16:2425- 2437, 2010.
First published on: April 15, 2009
Last modified on: August 30, 2011